In a recent study we found that 10 ppb dimethylnitrosamine given in the drinking water of strain A mice from preconception until 22 weeks of age caused a significant increase in lung tumors. We are repeating and extending this experiment to include longer endpoints in time, up to 28 months, so that effects of longer-term exposure to this amount of DMN can be determined. In a parallel investigation, we observed that treatment of pregnant mice with poly-chlorinated biphenyls resulted in a large increase in dimethylnitrosamine demethylase activity in the livers of their progeny before weaning. The effect was mediated largely by lactational delivery of the PCBs. In a tumorigenicity assay in progress, we are testing the effect of maternal treatment with PCBs on the carcinogenicity of DMN given to the offspring between birth and weaning. We also intend to measure DMN metabolism in other organs of the young mice, especially lung, pancreas, and kidney. Another possible environmental agent, N6(methylnitroso)adenosine, has been found to be a multipotential carcinogen in the mouse. We are studying the mechanism of its metabolic activation by high pressure liquid chromatography by determining and quantifying the types of products formed by different organ and subcellular preparations, the effect of inhibitors, etc. DNA modification experiments will also be attempted.